ADJUNCTIVE metformin at 2.0 g/day significantly improves BMI, insulin requirements, and lipid profiles in adolescents with Type 1 Diabetes (T1D), according to a new network meta-analysis.
Promising Role for Metformin in Adolescent T1D
Managing T1D in adolescents is increasingly complex due to the frequent presence of insulin resistance, dyslipidaemia, and early cardiovascular risk. While metformin is sometimes used off-label alongside insulin, optimal dosing for this age group has remained unclear. A new Bayesian network meta-analysis (NMA) of 764 adolescents aged 10–19 assessed the dose-dependent effects of metformin combined with insulin, comparing five regimens against placebo. Key endpoints included HbA1c, BMI, insulin dose, lipid levels, and adverse events, providing a robust overview of both efficacy and safety.
Metformin 2.0 g/day Leads in Weight and Lipid Outcomes
The highest fixed dose of metformin (2.0 g/day) outperformed other regimens in reducing BMI (mean difference −0.6 kg/m²) and LDL cholesterol (−12.78 mg/dL) compared with placebo. Improvements were also seen in total cholesterol with this dose and with a 50 kg weight-based regimen. Notably, however, no dose significantly improved HbA1c or triglycerides, suggesting limited glycaemic benefit. Daily insulin requirements were significantly reduced with 1.0 g/day, 2.0 g/day, and the ≥60 kg weight-based regimen. SUCRA rankings supported 2.0 g/day as the most effective overall in terms of metabolic improvement.
Favourable Safety Profile Across All Doses
Importantly, metformin demonstrated a reassuring safety profile in this cohort. Rates of gastrointestinal side effects, hypoglycaemia, diabetic ketoacidosis, and liver enzyme elevations were comparable to placebo across all dosing strategies. These findings address a key concern in paediatric diabetes management, balancing efficacy with tolerability, highlighting that higher doses may be used safely under clinical supervision.
In summary, adjunctive metformin at 2.0 g/day may offer a practical strategy to improve cardiometabolic outcomes in adolescents with T1D, supporting its consideration as a therapeutic adjunct. Further research is warranted to evaluate long-term outcomes and real-world applicability.
Reference
Li C et al. Efficacy and safety of variable-dose metformin as adjunctive therapy to insulin in adolescents with type 1 diabetes mellitus: a systematic review and network meta-analysis. BMC Endocr Disord. 2025;25(1):224.
